The A-helical amphipathic peptide D-(KLAKLAK) 2 is toxic to eukaryotic cells if internalized by a suitable targeting mechanism. We have targeted this peptide to malignant hemopoietic cells via conjugation to monoclonal antibodies, which recognize lineage-specific cell surface molecules. An anti-CD19/peptide conjugate efficiently killed 3/3 B lymphoid lines. However, an anti-CD33/peptide conjugate was cytotoxic to only one of three CD33-positive myeloid leukemia lines. The IC 50 towards susceptible lines were in the low nanomolar range. Conjugates were highly selective and did not kill cells that did not express the appropriate cell surface cognate of the antibody moiety. Anti-CD19/ peptide conjugates efficiently killed cells from patients with chronic lymphocytic leukemia but anti-CD33/peptide reagents were less effective against fresh acute myeloid leukemia cells. We therefore suggest that amphipathic peptides may be of value as targeted therapeutic agents for the treatment of a subset of hematologic malignancies.

Primary lymphoma of bone is extremely rare. There are increasing reports of lymphoma arising in bone adjacent to metallic prostheses. Herein, we describe the case of a 76-year-old man who developed diffuse large B cell lymphoma in the tibia 3 years after total knee arthroplasty for osteoarthritis. A review of the literature has identified 11 other cases of lymphoma arising in the context of orthopaedic metallic implants. To our knowledge this is the first reported case of a primary lymphoma arising in bone adjacent to a knee prosthesis. Possible pathogenetic mechanisms may include chronic antigenic stimulation of lymphocytes, proliferation of EBV-infected B lymphocytes, and direct mutagenic effects of metallic ions. Further research is required to investigate this intriguing link between metallic orthopaedic prostheses and localized lymphoma.

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Hypereosinophilia may be associated with any of several underlying diseases. Atopy or allergic drug reactions are the most common causes, but infections with bacteria and parasites should also be considered in the differential diagnosis. When thorough evaluation of a patient with chronic hypereosinophilia fails to reveal an underlying disease, the diagnosis of idiopathic hypereosinophilic syndrome (HES) should be considered. We report a patient with unexplained persistent hypereosinophilia associated with a chronic pruritic rash and an underlying diagnosis of HES (lymphocytic variant).

A 65-year-old woman with a 15-year history of urticaria pigmentosa on her trunk, arms, and legs was referred for further investigation when she was found to have elevation of the serum tryptase to 190 lg/l (normal range 2-14). She had noticed worsening of her skin lesions but was otherwise in good health. A blood count, blood film, and liver and renal function tests were normal. A bone marrow aspirate showed significant numbers of cytologically abnormal mast cells. Many of these had long and elegant tails, sometimes even three per cell (top left Image). Some of the spindle shaped cells (bottom left Image) and other mast cells (right Images) were hypogranular. A morphological diagnosis of systemic mastocytosis was confirmed by demonstration of a KIT D816V mutation in bone marrow cells.Neoplastic mast cells may be undetectable in bone marrow aspirates from patients with systemic mastocytosis, even when trephine biopsy sections show significant infiltration. When present, they are usually cytologically abnormal so that the diagnosis can be made from marrow films. Hypogranular-and spindle-shaped cells are characteristic. In addition, there may be aberrant expression of CD2 and CD25 and when mast cells are present in significant numbers in the aspirate a KIT mutation, usually KIT D816V, is likely to be detected.

A bone marrow examination in a young woman with anemia and β-thalassemia trait showed dyserythropoiesis in less than 10% of erythroblasts without other myelodysplastic changes, and cytogenetic analysis revealed trisomy of chromosome 8. Although she did not fulfill the current World Health Organization (WHO) criteria for diagnosis of a myelodysplastic syndrome, her acquired bone marrow disorder behaved as such, and she later developed acute myeloid leukemia.

A subset of variant histological patterns of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) has been associated with advanced disease stage and increased recurrence risk. Histopathology reports on core needle (CNB) and/or surgical excision biopsies (SEB) for 33 adult patients with NLPHL were examined for variant histology prevalence and association with disease stage and clinical outcome. Variant histological pattern was present in 13/33 patients (39%). Obtained tissue was inadequate for diagnosis in 1/23 (4.3%) cases of CNB. Variant histology was associated with stage IV disease at presentation (p<0.001). While SEB should be the procedure of choice in workup of patients for a diagnosis of NLPHL, CNB is an alternate option when SEB is contraindicated or difficult to undertake. Diagnostic reports should specifically note presence of variant histological patterns. Although late-stage disease was associated with progression or recurrence, overall prognosis is excellent for patients with NLPHL.